Beyond neuronal replacement: Embryonic retinal cells protect mature retinal neurons

Since the neurons of the retina are unable to be replaced naturally by the body, cellular replacement therapies have been widely pursued as treatments for degenerative retinal diseases such as glaucoma and macular degeneration. However, given the complexity of developmental cues required to properly specify particular cells types and our limited understanding thereof, feasible replacement strategies are in their infancy. An example of tightly regulated fate specification is the type-II cholinergic amacrine cell. We found that during a brief time in development the fate of the type-II cholinergic amacrine cell is dependent upon appropriate levels of cholinergic signaling. There is a paucity of neuron replacement studies in models of glaucoma where the retinal ganglion cells are lost. The replacement of ganglion cells may prove to be very challenging given the complex phenotype of these neurons. Therefore, neuroprotective therapies may be more beneficial to treat diseases where ganglion cells die. In several photoreceptor replacement studies there is evidence that eyes containing transplants had preserved visual function. However, very few of these studies showed convincing evidence of neuronal replacement; transplanted cells migrated into the retina, but failed to express neuronal markers. It is theorized that the maintained visual function result from neuroprotective factors released by the transplanted cells. We therefore sought to determine if transplanted embryonic retinal cells can protect ganglion cells from cholcicine-mediated death. We also investigated whether the developmental stage of the transplant was a factor that affected the neuroprototective capacity of these cells. We found that transplanted embryonic retina from embryonic day ten elicited the greatest neuroprotective effects. Additionally, we determined that the transplanted embryonic retina cells failed to differentiate as retinal neurons within the mature retina.